Is VAV1 p.Arg90= (c.268C>A) pathogenic?

VAV1 p.Arg90= (c.268C>A) is classified Likely benign in VAV1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). Very rare (popmax 0.00424%, nfe).

How common is VAV1 p.Arg90= (c.268C>A) in the general population?

VAV1 p.Arg90= (c.268C>A) is very rare (popmax 0.00424%, nfe) (gnomAD).

VAV1 p.Arg90=

c.268C>A · rs774093642 · VCV1945397

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00424%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.81	GERP -3.6, phastCons 0.002
Overall
CADD	6.881	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00424% European (non-Finnish) · 50/1,180,044 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.00322% 52/1,614,100 alleles · very rare exomes 51/1,461,876 · genomes 1/152,224 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00424%	23,601
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00133%	74,930

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: VAV1
Protein: p.Arg90=
Coding: c.268C>A
MANE Select: NM_005428
dbSNP: rs774093642
Type: single nucleotide variant
Location: chr19:6820765 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.63 · 10 PDB
Residue 90: the calponin-homology (ch) domain; a turn

Full VAV1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VAV1 p.Arg90Gln Uncertain significance ★ ⚠ same residue
VAV1 p.Arg90Trp Uncertain significance ★ ⚠ same residue
VAV1 p.Ala168Val Uncertain significance ★★ ⚠ same type
VAV1 p.Ala362Thr Uncertain significance ★★ ⚠ same type
VAV1 p.Ala734Thr Uncertain significance ★★ same type
VAV1 p.Arg15Gln Uncertain significance ★★ ⚠ same type
VAV1 p.Arg179Ser Uncertain significance ★★ ⚠ same type
VAV1 p.Arg195His Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/vav1-p-arg90 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown